It has been reported that the number of diabetics has increased to 10.5 % of the global adult population (∼ 537 million) [1]. As a complex metabolic disease, diabetes is associated with many serious complications. A diabetic patient has a 15–20 % lifetime risk of developing diabetic foot ulcer [2]. Diabetic ulcer is a common type of chronic wound ulcer that affects patients' quality of life and requires costly treatment [3]. Diabetic ulcer has an exceptionally complex pathology due to persistent hyperglycemia and associated diabetic complications [4]. After bacterial colonization and biofilm formation, diabetic wounds will exhibit drug resistance [5], which may further lead to significant morbidity and mortality [6,7]. Therefore, the development of effective treatment for diabetic wounds is in high demand in clinical practice.

In the past few decades, diabetic wounds were usually treated with dry dressings such as bandages and gauze to absorb wound exudates and prevent infection [8,9]. However, they generally act as physical barriers, which fail to meet the requirements of the entire diabetic wound healing process [10,11]. Wound management presents a substantial challenge in maintaining wet conditions at the wound site [12,13]. It is generally recognized that an optimal condition for tissue regeneration should maintain a balanced moisture level, neither flooded with wound exudates nor dried out due to an insufficient wet supply [14,15]. Hydrogels have an inherent advantage over other wound dressing materials due to their physical and chemical properties that mimic the extracellular matrix (ECM) [[16], [17], [18]]. Hence, as an excellent candidate, different hydrogels were developed to prevent bacterial infection in diabetic wound [19]. Although great progress have been made, exploring multifunctional hydrogels for synergistic treatment of inflammatory reactions and bacterial infections in diabetic wounds are critical.

Hydrogen sulfide (H2S) plays a critical regulatory role in physiological and pathological processes [20,21]. It is reported that H2S regulates inflammation, oxidative stress, and angiogenesis [22,23], suggesting that enhanced endogenous H2S production or exogenous H2S supplementation may promote the healing of diabetic trauma [[24], [25], [26]]. Fortunately, as a 3D matrix, hydrogels can easily load H2S donors to improve the microenvironment of diabetic wounds [[27], [28], [29]]. For example, Yuan and Shen group reported keratin-based hydrogel for effective diabetic wound healing [[30], [31], [32]]. However, most hydrogels loaded with H2S donors involves complex composition, multi-step preparation and explosive release of H2S, resulting in high cost, complex synthesis and local toxicity [[33], [34], [35], [36]]. Hence, design multifunctional H2S-based hydrogels with facile preparation and high performance for diabetic wounds is still a challenge.

Bis[tetrakis(hydroxymethyl)phosphonium]sulfate solution (THPS) is an environmentally friendly cationic phosphate fungicide [37,38]. It can significantly inhibit the growth of fungal algae and bacteria, destroy bacterial biofilms, and hardly cause bacterial resistance [39]. Importantly, it can be rapidly degraded into harmless substances [40]. Given these advantages, THPS can be used as a perfect substitute for antibiotics [41]. Recently, Ouyang, J et al. reported that bovine serum albumin (BSA) composed of many different amino acids could react with THPS through Mannich reaction to form antibiotic-free hydrogel with excellent biocompatibility [42]. In addition to these, BSA‑gold nanoclusters (BSA-AuNCs) are a kind of nanomaterial with simulated enzyme catalytic activities [43,44]. Due to their excellent physicochemical properties [45], BSA-AuNCs have gradually become an important member of the nanozyme field. We suppose that AuNCs would catalyze sulfur element in BSA to produce H2S when THPS and BSA-AuNCs were mixed together to form hydrogel.

Based on the above consideration, an antibiotic-free antibacterial protein hydrogel with self-generating H2S gas (H2S-Hydrogel) was rationally fabricated for the first time. Notably, several advantages of the H2S-Hydrogel make them particularly attractive. First, it is prepared by simply mixing BSA-AuNCs with THPS at room temperature for a few minutes (Fig. 1). Second, H2S-Hydrogel with Au nanozyme-mediated self-generation of H2S is proposed for the first time, which opens a new perspective of H2S donors. Third, the prepared H2S-Hydrogel with good adhesion and biocompatibility has a high antibacterial activity against Staphylococcus aureus (S. aureus), Escherichia coli (E.coli), Pseudomonas aeruginosa (P.aeruginosa) and even bacterial biofilms. Last, H2S-Hydrogel can promote angiogenesis and re-epithelization of diabetic wounds, and reduce inflammation and oxidative stress. It provides a new platform for the design and preparation of smart wound dressing in clinics.